What is spinal muscular atrophy?

Spinal muscular atrophy is a group of inherited disorders that cause progressive muscle degeneration and weakness. Spinal muscular atrophy (SMA) is the second leading cause of neuromuscular disease. It is usually inherited as an autosomal recessive trait (a person must get the defective gene from both parents to be affected).

There are several types of SMA called subtypes. Each of the subtypes is based on the severity of the disorder and the age at which symptoms begin. There are three types of SMA that affect children before the age of 1 year. There are two types of SMA, type IV and Finkel type, that occur in adulthood, usually after age 30. Symptoms of adult-onset spinal muscular atrophy are usually mild to moderate and include muscle weakness, tremor and twitching.

The prognosis for individuals with SMA varies depending on the type of SMA and the degree of respiratory function. The patient's condition tends to deteriorate over time, depending on the severity of the symptoms.

What are the symptoms of spinal muscular atrophy?

Three types of SMA affect children before age one year. Type 0 is the most severe form of spinal muscular atrophy and begins before birth. Usually, the first symptom of type 0 is reduced movement of the fetus that is first seen between 30 and 36 weeks of the pregnancy. After birth, these newborns have little movement and have difficulties with swallowing and breathing.

Type I spinal muscular atrophy (called Werdnig-Hoffman disease) is another severe form of SMA. Symptoms of type 1 may be present at birth or within the first few months of life. These infants usually have difficulty breathing and swallowing, and they are unable to sit without support.

Children with type II SMA usually develop muscle weakness between ages 6 and 12 months. They cannot stand or walk without help.

Type III SMA (called Kugelberg-Welander disease or juvenile type) is a milder form of SMA than types 0, I or II. Symptoms appear between early childhood (older than age 1 year) and early adulthood. Individuals with type III SMA are able to stand and walk without help. They usually lose their ability to stand and walk later in life.
There are two other types of spinal muscular atrophy, type IV and Finkel type that occur in adulthood, usually after age 30. Symptoms of adult-onset SMA are usually mild to moderate and include muscle weakness, tremor and twitching.

How is spinal muscular atrophy diagnosed?

To make a diagnosis of SMA, symptoms need to be present. When symptoms are present, diagnosis can be made by genetic testing. Gene alterations (mutations) in the SMN1 and VAPB genes cause SMA. Having extra copies of the SMN2 gene can modify the course of SMA.

Genetic testing on a blood or tissue sample is done to identify whether there is at least one copy of the SMN1 gene by looking for its special makeup. Mutations in the SMN1 gene cause types 0, I, II, III, and IV. Some people who have SMA type II, III, or IV have three or more copies of the SMN2 gene. Having these extra copies can modify the course of SMA. The more copies of SMN2 gene a person has, the less severe his or her symptoms.

Genetic testing for a mutation in the VAPB gene is done to diagnose the Finkel type SMA.

In some situations other tests such as an EMG electromyography (EMG) or muscle biopsy may be needed because it is not possible to conduct the SMN gene tests or no abnormality is identified.

What is the treatment for spinal muscular atrophy?

There is currently no specific cure for SMA. Infants who have a severe form of SMA frequently die of respiratory failure due to weakness of the muscles that help with breathing. Children who have milder forms of SMA will live much longer but they may need extensive medical support.

The current treatment for SMA involves prevention and management of the secondary effect of muscle weakness and loss.

Today, much can be done for SMA patients in terms of medical and in particular respiratory, nutritional and rehabilitation care. In addition, several drugs have been identified in laboratory experiments that may help patients. Some of the drugs that are currently being investigated include: Butyrates, valproic acid, hydroxyurea, and riluzole.

At present gene therapy - replacing the altered genes with a normal version ? is being tested in animals. Researchers believe that gene replacement for SMA will take many more years of research before it can be used in humans. Other approaches to developing better treatment include searching for drugs that increase SMN levels, enhance residual SMN function, or compensate for its loss.

Is spinal muscular atrophy inherited?

SMA types 0, I, II, III, and IV are inherited in an autosomal recessive pattern in families. In autosomal recessive inheritance, a person who has SMA has inherited two altered (mutated) copies of the SMN1 gene from his or her parents. The parents of an individual with an autosomal recessive inherited disorder such as SMA are carriers of one copy of the altered gene. Since they carry a normal version of the gene they do not have signs or symptoms of the disorder.

Finkel type SMA is inherited in an autosomal dominant pattern. This means that the person has one copy of the altered gene in each cell that causes the disorder.

Project Cure SMA [projectcuresma.org]
A collaborative initiative between Families of SMA and clinical investigators designed to help facilitate the rapid translation of promising new therapies to individuals with SMA.

International Spinal Muscular Atrophy Patient Registry [fsma.org]A resource by which individuals and families affected by SMA and researchers interested in studying SMA can come into contact with one another. The registry is coordinated by the Department of Medical and Molecular Genetics Department at Indiana University and fully funded by Families of SMA.

Muscular Dystrophy Association - USA [mda.org]A national voluntary health agency dedicated to conquering more than 40 neuromuscular diseases that affect a million Americans of all ages.

Spinal Muscular Atrophy Foundation [smafoundation.org] The Spinal Muscular Atrophy Foundation is working to accelerate the development of a treatment or a cure for SMA, the number one genetic killer of infants and toddlers.